دورية أكاديمية
Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
| العنوان: | Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology |
|---|---|
| المؤلفون: | Wouter van Rheenen, Rick A. A. van der Spek, Mark K. Bakker, Joke J. F. A. van Vugt, Paul J. Hop1, Ramona A. J. Zwamborn, Niek de Klein, Harm-Jan Westra, Olivier B. Bakker, Patrick Deelen, Gemma Shireby, Eilis Hannon, Matthieu Moisse, Denis Baird, Restuadi Restuadi, Egor Dolzhenko, Annelot M. Dekker, Klara Gawor, Henk-Jan Westeneng, Gijs H. P. Tazelaar, Kristel R. van Eijk, Maarten Kooyman, Ross P. Byrne, Mark Doherty, Mark Heverin, Ahmad Al Khleifat, Alfredo Iacoangeli, Aleksey Shatunov, Nicola Ticozzi, Johnathan Cooper-Knock, Bradley N. Smith, Marta Gromicho, Siddharthan Chandran, Suvankar Pal, Karen E. Morrison, Pamela J. Shaw, John Hardy, Richard W. Orrell, Michael Sendtner, Thomas Meyer, Nazli Başak, Anneke J. van der Kooi, Antonia Ratti, Isabella Fogh, Cinzia Gellera, Giuseppe Lauria Pinter, Stefania Corti, Cristina Cereda, Daisy Sproviero, Sandra D’Alfonso, Gianni Sorarù, Gabriele Siciliano, Massimiliano Filosto, Alessandro Padovani, Adriano Chiò, Andrea Calvo, Cristina Moglia, Maura Brunetti, Antonio Canosa, Maurizio Grassano, Ettore Beghi, Elisabetta Pupillo, Giancarlo Logroscino, Beatrice Nefussy, Alma Osmanovic, Angelica Nordin, Yossef Lerner, Michal Zabari, Marc Gotkine, Robert H. Baloh, Shaughn Bell, Patrick Vourc’h, Philippe Corcia, Philippe Couratier, Stéphanie Millecamps, Vincent Meininger, François Salachas, Jesus S. Mora Pardina, Abdelilah Assialioui, Ricardo Rojas-García, Patrick Dion, Jay P. Ross, Albert C. Ludolph, Jochen H. Weishaupt, David Brenner, Axel Freischmidt, Gilbert Bensimon, Alexis Brice, Alexandra Dürr, Christine A. M. Payan, Safa Saker-Delye, Nicholas Wood, Simon Topp, Rosa Rademakers, Lukas Tittmann, Wolfgang Lieb, Andre Franke, Stephan Ripke, Alice Braun, Julia Kraft, David C. Whiteman, Catherine M. Olsen, Andre G. Uitterlinden, Albert Hofman, Marcella Rietschel, Sven Cichon, Markus M. Nöthen, Philippe Amouyel, SLALOM Consortium, PARALS Consortium, SLAGEN Consortium, SLAP Consortium, Bryan J. Traynor, Andrew B. Singleton, Miguel Mitne Neto, Ruben J. Cauchi, Roel A. Ophoff, Martina Wiedau-Pazos, Catherine Lomen-Hoerth, Vivianna M. van Deerlin, Julian Grosskreutz, Annekathrin Rödiger, Nayana Gaur, Alexander Jörk, Tabea Barthel, Erik Theele, Benjamin Ilse105, Beatrice Stubendorff105, Otto W. Witte105, Robert Steinbach 105, Christian A. Hübner107, Caroline Graff108, Lev Brylev, Vera Fominykh, Vera Demeshonok112, Anastasia Ataulina109, Boris Rogelj, Blaž Koritnik 116, Janez Zidar116, Metka Ravnik-Glavač117, Damjan Glavač118, Zorica Stević119, Vivian Drory44, 120, Monica Povedano61, Ian P. Blair, Matthew C. Kiernan122, Beben Benyamin10, 123, Robert D. Henderson124, 125, Sarah Furlong, Susan Mathers, Pamela A. McCombe, Merrilee Needham, Shyuan T. Ngo, Garth A. Nicholson, Roger Pamphlett, Dominic B, Frederik J. Steyn, Kelly L. Williams, Karen A. Mather, Perminder S. Sachdev, Anjali K. Henders, Leanne Wallace, Mamede de Carvalho, Susana Pinto20, Susanne Petri, Markus Weber, Guy A. Rouleau, Vincenzo Silani, Charles Curtis, Gerome Breen, Jonathan Glass, Robert H. Brown, John E. Landers, Christopher E. Shaw, Peter M. Andersen, Ewout J. N. Groen, Michael A. van Es, R. Jeroen Pasterkamp, Dongsheng F, Fleur C. Garton, Allan F. McRae, George Davey Smith, Tom R. Gaunt, Michael A. Eberle, Jonathan Mill, Russell L. McLaughlin, Orla Hardiman, Kevin P. Kenna, Naomi R. Wray, Ellen Tsai, Heiko Runz, Lude Franke, Ammar Al-Chalabi, Philip Van Damme, Leonard H. van den Berg, Jan H. Veldink Vincenzo Silani, Isabella F, Cinzia Tiloca, Silvia Peverelli, Franco Taroni, Viviana Pensato, Barbara Castellotti, Giacomo P. Comi, Roberto Del Bo, Mauro Ceroni, Stella Gagliardi, Lucia Corrado, Letizia Mazzini, Flavia Raggi, Costanza Simoncini, Annalisa Lo Gerfo, Maurizio Inghilleri, Alessandra Ferlini |
| المساهمون: | van Rheenen, Wouter, van der Spek, Rick A. A., Bakker, Mark K., van Vugt, Joke J. F. A., Hop1, Paul J., Zwamborn, Ramona A. J., de Klein, Niek, Westra, Harm-Jan, Bakker, Olivier B., Deelen, Patrick, Shireby, Gemma, Hannon, Eili, Moisse, Matthieu, Baird, Deni, Restuadi, Restuadi, Dolzhenko, Egor, Dekker, Annelot M., Gawor, Klara, Westeneng, Henk-Jan, Tazelaar, Gijs H. P., van Eijk, Kristel R., Kooyman, Maarten, Byrne, Ross P., Doherty, Mark, Heverin, Mark, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Shatunov, Aleksey, Ticozzi, Nicola, Cooper-Knock, Johnathan, Smith, Bradley N., Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E., Shaw, Pamela J., Hardy, John, Orrell, Richard W., Sendtner, Michael, Meyer, Thoma, Başak, Nazli, van der Kooi, Anneke J., Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria Pinter, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, D’Alfonso, Sandra, Sorarù, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chiò, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Canosa, Antonio, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H., Bell, Shaughn, Vourc’H, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stéphanie, Meininger, Vincent, Salachas, Françoi, Mora Pardina, Jesus S., Assialioui, Abdelilah, Rojas-García, Ricardo, Dion, Patrick, Ross, Jay P., Ludolph, Albert C., Weishaupt, Jochen H., Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexi, Dürr, Alexandra, Payan, Christine A. M., Saker-Delye, Safa, Wood, Nichola, Topp, Simon, Rademakers, Rosa, Tittmann, Luka, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, Kraft, Julia |
| سنة النشر: | 2021 |
| المجموعة: | Sapienza Università di Roma: CINECA IRIS |
| مصطلحات موضوعية: | genome-wide association study, ALS, gene, autophagy |
| الوصف: | Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/wos/WOS:000727387900007; numberofpages:28; journal:NATURE GENETICS; http://hdl.handle.net/11573/1587553Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85122277130 |
| الإتاحة: | http://hdl.handle.net/11573/1587553Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.DD5346FF |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |